Biology subjects

Dworkin, S.

Publications and source records attributed to Dworkin, S..

4 recordsLinked to original sources

bioRxiv2026

A flexible diet platform for the nutrigenomic screening of Drosophila disease models

Nutrient-gene interactions shape metabolic disease phenotypes, but systematic testing is limited by the effort required to produce defined diets. We developed a flexible protocol that assembles precisely defined synthetic diets for Drosophila melanogaster from individual stock solutions. Using this approach, we generated a rational array of 51 single-nutrient-varied diets and demonstrated that flexible and standard preparation methods produce comparable developmental timing, survival, adult body weight, and starvation resistance in wildtype flies. Applying the dietary array to a Drosophila model of isolated sulfite oxidase deficiency, a severe condition caused by impaired sulfur amino acid catabolism, revealed nutrient-specific effects on pupal survival and pupariation timing, including rescue by cysteine depletion and other amino acid modified diets. This platform provides a scalable in vivo framework for mapping genotype-specific nutritional responses across Drosophila disease models. Key pointsO_LIDeveloped a flexible platform for assembling precisely defined synthetic diets in Drosophila. C_LIO_LIGenerated a rational 51-diet array, enabling scalable nutrigenomic screening. C_LIO_LIFlexible and standard diet preparations yielded matching developmental and adult fitness outcomes. C_LIO_LIDietary array screening in a sulfite oxidase deficiency model recapitulated cysteine sensitivity and identified novel nutrient modifiers. C_LI

genetics↗

bioRxiv2025

SAMBA: A Segment Anything Model-based tool for semi-automated Behavioural Analysis of Drosophila and other model organisms

Quantitative behavioural analysis is a powerful approach for linking genotype to phenotype, but many existing tools require specialised hardware, extensive preprocessing, or coding expertise. We present SAMBA (Segment Anything Model for Behavioural Analysis), an open-access, Google Colab-based pipeline that harnesses the Segment Anything Model 2 (SAM2) for accurate, semi-automated tracking without thresholding or background subtraction. With minimal user input, SAMBA extracts movement parameters, detects behavioural states, and supports batch processing. Validating SAMBA in a Drosophila melanogaster model of 3-hydroxyisobutyryl-CoA hydrolase (HIBCH) deficiency revealed impaired locomotion, reduced speed, and altered decision-making, highlighting its ability to capture nuanced phenotypes in neurometabolic disease. We further demonstrate adaptability to adult Drosophila and larval zebrafish, underscoring its cross-species utility. By combining foundation-model segmentation with an accessible interface, SAMBA lowers technical barriers to high-throughput behavioural phenotyping and is readily extendable to diverse model organisms, life stages, and experimental paradigms. This flexibility positions SAMBA as a valuable platform for accelerating disease mechanism studies, genetic screens, and preclinical testing. SUMMARY STATEMENTWe present an easy-to-use, open-access tool designed for Drosophila larval movement analysis, and readily customised for other applications, enabling rapid, scalable assessment of organism behaviour without specialised equipment or coding expertise.

animal behavior and cognition↗

bioRxiv2024

Testicular sex cord stromal tumors in mice with constitutive activation of PI3K and loss of Pten

Testicular tumors are the most common malignancy of young men and tumors affecting the testis are caused by somatic mutations in germ or germ-like cells. The PI3K pathway is constitutively activated in about one third of testicular cancers. To investigate the role of the PI3K pathway in transforming stem-like cells in the testis, we investigated tumors derived from mice with post-natal, constitutive activation of PI3K signaling and homozygous deletion of tumor suppressor Pten, targeted to nestin expressing cells. Mice developed aggressive tumors, exhibiting heterogeneous histopathology and hemorrhaging. The tumors resemble the rare testis tumor type, testicular sex cord-stromal Leydig cell tumors. Single cell resolution spatial tissue analysis demonstrated that T-cells are the dominant tumor infiltrating immune cell type, with very few infiltrating macrophages observed in the tumor tissue, with CD8+ T-cells predominating. Further analysis showed that immune cells preferentially localize to or accumulate within stromal regions. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=114 SRC="FIGDIR/small/613175v1_ufig1.gif" ALT="Figure 1"> View larger version (37K): org.highwire.dtl.DTLVardef@657f74org.highwire.dtl.DTLVardef@192bcc7org.highwire.dtl.DTLVardef@a7c63eorg.highwire.dtl.DTLVardef@c81d17_HPS_FORMAT_FIGEXP M_FIG C_FIG

cancer biology↗

bioRxiv2024

Valine restriction extends survival in a Drosophila model of short-chain enoyl-CoA hydratase 1 (ECHS1) deficiency

Short-chain enoyl-CoA hydratase 1 deficiency (ECHS1D) is a rare genetic disorder caused by biallelic pathogenic variants in the ECHS1 gene. ECHS1D is characterised by severe neurological and physical impairment that often leads to childhood mortality. Therapies such as protein and single nutrient-restricted diets show poor efficacy, whereas development of new treatments is hindered by the low prevalence of the disorder and a lack of model systems for treatment testing. Here we report on the establishment of a Drosophila model of ECHS1D. Flies carrying mutations in Echs1 (CG6543) were characterised for their physical and metabolic phenotypes, and dietary intervention to improve fly model health was explored. The Echs1 null larvae recapitulated human ECHS1D phenotypes including elevated biomarkers (S-(2-carboxypropyl)cysteamine and 2,3-dihydroxy-2-methylbutyric acid), poor motor behaviour and early mortality, and could be rescued by expression of a human ECHS1 transgene. We observed that both restriction of valine in isolation, or all branched-chain amino acids (BCAAs - leucine, isoleucine, and valine) together, extended larval survival, supporting the idea that reducing BCAA pathway catabolic flux is beneficial in this disorder. Further, metabolic profiling revealed substantial changes to carbohydrate metabolism, suggesting that Echs1 loss causes widespread metabolic dysregulation beyond valine metabolism. The similarities between Drosophila and human ECHS1D suggest that the fly model is a valuable animal system in which to explore mechanisms of pathogenesis and novel treatment options for this disorder.

genetics↗